STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters.

Abstract:

:Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.

journal_name

Nat Commun

journal_title

Nature communications

authors

Boudewijns R,Thibaut HJ,Kaptein SJF,Li R,Vergote V,Seldeslachts L,Van Weyenbergh J,De Keyzer C,Bervoets L,Sharma S,Liesenborghs L,Ma J,Jansen S,Van Looveren D,Vercruysse T,Wang X,Jochmans D,Martens E,Roose K,De Vlie

doi

10.1038/s41467-020-19684-y

subject

Has Abstract

pub_date

2020-11-17 00:00:00

pages

5838

issue

1

issn

2041-1723

pii

10.1038/s41467-020-19684-y

journal_volume

11

pub_type

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